The goals of the proposed research are to develop libraries of potential inhibitors for both HIV reverse transcriptase (HIV-RT) and HIV integrase HIV-IN enzymes. The libraries will be created using a common Horner-Emmons-Wittig reagent developed in applicant's laboratories. This reagent provides a rapid synthetic sequence into three diverse classes of compounds including: 1. Symmetrical and unsymmetrical disulfones based on known catechol HIV-IN inhibitors, 2. Novel isosteric analogs of nucleoside triphosphates as HIV-RT inhibitors, and 3. Non-nucleoside HIV-RT inhibitors. The specific aims are: (a) To synthesize and test novel 5'-disulfone-monophosphate isosteres of nucleic acid triphosphates as nucleoside HIV-RT inhibitors; (b) To synthesize and test a library of gem-disulfone linked aryl acids as non-nucleoside HIV-RT inhibitors; (c) To synthesize and test a gem-disulfone linked library of catechol analogs as HIV-IN inhibitors; (d) To synthesize and test possible bifunctional HIV-IN/HIV-RT inhibitors; (e) To synthesize and test potential suicide inhibitors. We are uniquely positioned to rapidly synthesize a large number of compounds. The investigators have prepared two compounds that show micromolar inhibition of HIV-IN. Testing of these compounds was done at NIH using standard assays. A letter of collaboration to test future HIV-IN inhibitors is attached. Testing for HIV-RT inhibition will be done in their laboratory using the NEN Lifesciences RT-Detect Reverse Transcriptase Assay Kit (CAT. #NEK-070).